A Comprehensive Review of Dysregulated miRNAs Involved in Cervical Cancer

Abstract

MicroRNAs(miRNAs) have become the center of interest in oncology. In recent years, various studies have demonstrated that miRNAs regulate gene expression by influencing important regulatory genes and thus are responsible for causing cervical cancer. Cervical cancer being the third most diagnosed cancer among the females worldwide, is the fourth leading cause of cancer related mortality. Prophylactic human papillomavirus (HPV) vaccines and new HPV screening tests, combined with traditional Pap test screening have greatly reduced cervical cancer. Yet, thousands of women continue to be diagnosed with and die of this preventable disease annually. This has necessitated the scientists to ponder over ways of evolving new methods and chalk out novel treatment protocols/strategies. As miRNA deregulation plays a key role in malignant transformation of cervical cancer along with its targets that can be exploited for both prognostic and therapeutic strategies, we have collected and reviewed the role of miRNA in cervical cancer. A systematic search was performed using PubMed for articles that report aberrant expression of miRNA in cervical cancer. The present review provides comprehensive information for 246 differentially expressed miRNAs gathered from 51 published articles that have been implicated in cervical cancer progression. Of these, more than 40 miRNAs have been reported in the literature in several instances signifying their role in the regulation of cancer. We also identified 40 experimentally validated targets, studied the cause of miRNAs dysregulation along with its mechanism and role in different stages of cervical cancer. We also identified and analysed miRNA clusters and their expression pattern in cervical cancer. This review is expected to further enhance our understanding in this field and serve as a valuable reference resource.

Keywords: Cervical cancer; Cervical intraepithelial neoplasia.; miRNA; miRNA cluster; miRNA targets.

Fig. (1)

Number of dysregulated miRNAs repeated in papers.

Fig. (2)

Location of each dysregulated miRNA in human chromosomes.

Fig. (3)

Region wise distribution of miRNAs.

Fig. (4)

Shows numbers of oncomiRs, tumor supressors and miRNAs that can function as either an oncomiR or a tumor suppressor.

Fig. (5)

Expression profile analysis of miRNAs dysregulated in cervical cancer.

Fig. (6)

Depicts different causes of miRNA dysregulation.

Fig. (7)

Network for miRNAs and their targets involved in apoptosis in cervical cancer. Legend:

Fig. (8)

Cell cycle regulation by miRNA and their targets dysregulated in cervical cancer. Legend: ↑ represents upregulation, ↓ represents downregulation, ┬ represents unknown pathway.

Fig. (9)

Network for miRNAs involved in migration and invasion of cervical cancer cells. Legend: ↑ represents upregulation, ↓ represents downregulation, → represents unknown pathway.